Growing biochemical evidence suggests that cell membranes segregate their components into nanoscopic platforms or ?rafts? to control signaling and trafficking across the membrane. Signaling is a key function of the cell, and it is unsurprising that raft formation has been proposed to influence a wide range of diseases, such as Alzheimer?s, influenza, and diabetes. This project will shed further light on this issue by accomplishing 3 different aims. The development of a new microscopy technique capable of imaging membranes at nanometer scale and microsecond times- The limiting factor in current studies of lipid rafts is the limits of current imaging techniques. The characterization of model membranes at the nanoscale- Model membranes, composed of a just few components, will provide valuable information on the lipid interactions that drive the formation of lipid rafts Imaging live cells- Live cells will be imaged, and their nanoscale membrane structure correlated to the position of proteins known to associate with rafts. This will provide information on the actual behavior of cell membranes in organizing proteins. This project will answer questions about how cells are organized that will have immediate impact on the understanding of many diseases. This project will also develop tools that will enable many future experiments on how disease affects the functioning of a cell.